On December 5, 2019 Innovent Biologics, Inc. ("Innovent" or "the Company") (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, reported that the first patient has been successfully dosed in a Phase I clinical trial (CIBI110A101) of anti-lymphocyte activation gene 3 (LAG-3)recombinant fully human monoclonal antibody drug candidate (IBI110) in China (Press release, Innovent Biologics, DEC 5, 2019, View Source [SID1234551980]).

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CIBI110A101 is a phase I clinical study conducted in China to evaluate IBI110 in the treatment of patients with advanced malignancies. The primary objectives of the study are to evaluate the safety, tolerability, and initial anti-tumor efficacy of IBI110, either as monotherapy or in combination with Tyvyt (sintilimab injection), an anti-programmed cell death protein 1 (PD-1) antibody drug. The Phase Ia study will explore the safety, tolerability and efficacy of IBI110 as monotherapy.

IBI110 is a recombinant fully human anti-LAG-3 monoclonal antibody and will provide a brand new clinical solution to cancer patients. IBI110 can directly bind to LAG-3 on the surface of T cells, disturb the interaction between LAG-3 and MHCII, relieve the inhibiting effect of LAG-3 on T cells activation and enhance the anti-tumor immune response of T cells. Furthermore, the combination of anti-LAG-3 and anti-PD-1/PD-L1 may provide synergistic enhancement and improve the anti-tumor efficacy.

Professor Caicun Zhou, director of Oncology Department of Shanghai Pulmonary Hospital, said: "Although immune checkpoint inhibitors have shown gratifying progress in oncology therapy, we still confront many new challenges. With the increasing popularity of anti-PD-1/PD-L1 antibody, some patients have shown resistance to anti-PD-1/PD-L1 therapy. Meanwhile, the efficacy of anti-PD-1/PD-L1 therapy in its initial treatment of patients also needs to be further improved. Therefore, it has great significance to develop the next generation of tumor immune drugs, while LAG-3 is one of the most promising and prospective targets in tumor immunotherapy. We are looking forward to the clinical results of IBI110."

Dr. Hui Zhou, Vice President and Head of Oncology Strategy and Medical Sciences of Innovent, said: "LAG-3 is an important immuno-inhibitory receptor, but there is no approved antibody drug targeting LAG-3 so far. Currently, a series of relevant clinical trials is ongoing abroad, and the preliminary results have shown certain safety and anti-tumor effectiveness of anti-LAG-3 antibody either as monotherapy or combination with anti-PD-1/PD-L1 antibody. Notably, the combination therapies hopefully exhibited synergistic enhancement effect. Therefore, developing drugs targeting LAG-3 may provide more novel, comprehensive and effective treatments for patients. We will evaluate the potential clinical value of IBI110 and its combination therapy, and hope to ultimately benefit more patients."

About IBI110

IBI110 is an innovative IgG4κ recombinant fully human anti-LAG-3 monoclonal antibody developed by Innovent. As class 1 innovative drug, IBI110 can directly bind to LAG-3 and block its interaction with MHCII, thus activate and enhance the anti-tumor immune response of T cells. Furthermore, IBI110 may synergize with anti-PD-1/PD-L1 antibody to improve the anti-tumor efficacy. IBI110 may hopefully exert antitumor activity and delay the drug resistance in the form of monotherapy or combination with Tyvyt (sintilimab injection), which will provide more effective treatments for cancer patients.

About CIBI110A101

CIBI110A101 is a Phase I clinical study conducted in China to evaluate IBI110 in the treatment of patients with advanced malignancies. The primary objectives of the study are to evaluate the safety, tolerability, and initial anti-tumor efficacy of IBI110, either as monotherapy or in combination with Tyvyt (sintilimab injection), an anti-programmed cell death protein 1 (PD-1) antibody drug.

On December 5, 2019 US Oncology reported during the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, principal investigators from The US Oncology Network (The Network) and US Oncology Research will demonstrate detailed results from more than 20 studies covering topics including lymphoma, multiple myeloma, leukemia and more (Press release, US Oncology, DEC 5, 2019, View Source [SID1234551978]). The ASH (Free ASH Whitepaper) Annual Meeting, a leading scientific event in malignant and non-malignant hematology, will be held December 7-10 at the Orange County Convention Center in Orlando.

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"The future of cancer treatment is being cultivated at many practices in the community setting," said Michael Seiden, MD, PhD, president of The US Oncology Network. "I’m proud of the work being done by research investigators in The US Oncology Network. It’s amazing to see the quality of their research presented at ASH (Free ASH Whitepaper) every year. Their innovations are truly making a difference that impact cancer patients now and in the future."

Jeff Sharman, MD, medical director of Hematology Research for The US Oncology Network and director of Research at Willamette Valley Cancer Institute and Research Center (WVCI), will present an oral abstract titled, "ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL)," on Saturday, December 7 at 7:30am ET in Hall D, Level 2.

"BTK inhibitors have revolutionized the treatment of CLL," said Dr. Sharman. "This study led to the FDA approval of acalabrutinib in previously untreated CLL and presents compelling evidence of both safety and efficacy of the drug. With a second approved BTK inhibitor in CLL, there are now more available options for patients in need of therapy."

Additionally, Dr. Sharman will share his expertise during an education program on indolent lymphomas. His presentation titled, "Targeting CD20: Teaching an Old Dog New Tricks," will take place Saturday, December 7, 2:00pm-3:30pm ET as well as Sunday, December 8, 9:30am-11:00am ET in Tangerine 1 (WF1), Level 2.

"CD20 is an established target for the treatment of both lymphoma and chronic lymphocytic leukemia," said Dr. Sharman. "For nearly 2 decades, rituximab was an unequaled therapeutic in this space as the standard of care. With novel subcutaneous formulations, biosimilar molecules, second generation anti-CD20 antibodies, immunologically synergistic combinations and novel bispecific approaches, CD20-directed therapies are undergoing a dramatic change."

Christopher Yasenchak, MD, associate chair of Hematology Research for The US Oncology Network and hematologist with WVCI, is presenting an oral abstract titled, "Phase 2 Study of Frontline Brentuximab Vedotin Plus Nivolumab in Patients with Hodgkin Lymphoma Aged ≥60 Years," on Saturday, December 7 at 2:30pm ET in W224, Level 2.

"Elderly patients with Classical Hodgkin Lymphoma experience markedly inferior outcomes with conventional chemotherapy when compared to younger patients. This is due to differences in disease biology, increased rates of advanced disease, medical co-morbidities and treatment-related morbidity and mortality. As such, novel treatment strategies are needed," said Dr. Yasenchak. "The combination of brentuximab vedotin and nivolumab delivered in the frontline setting shows a high response rate and improved toxicity profile. This regimen may fill an unmet need for elderly patients unfit for conventional chemotherapy."

Furthermore, Robert Rifkin, MD, FACP, medical director of Biosimilars for McKesson, associate chair of Hematology Research and myeloma disease lead for The US Oncology Network, and hematologist with Rocky Mountain Cancer Centers (RMCC), will present "Daratumumab (DARA) Maintenance Therapy Improves Depth of Response and Results in Durable Progression-Free Survival (PFS) Following Dara Plus Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) Induction Therapy in Multiple Myeloma (MM): Update of the Lyra Study." The oral presentation will take place Monday, December 9 at 5:30pm ET in Hall E2, Level 2.

"This is an important study for multiple myeloma patients treated in the community setting as it gives them a treatment option that is relatively non-toxic that may increase the depth of response and achieve durable remissions," said Dr. Rifkin. "Additionally, DARA-Cy-Bord is safe and easy to manage."

Physicians with US Oncology Research worked with McKesson Data, Evidence and Insights investigators on a real-world evidence (RWE) study titled, "Treatment Patterns and Outcomes of Patients with Relapsed Follicular Lymphoma Treated with Idelalisib in a Community Oncology Setting." The poster presentation will take place Sunday, December 8, 6:00pm-8:00pm ET in Hall B, Level 2.

"This study evaluated patient profiles, treatment patterns and clinical outcomes among adult patients with relapsed or refractory follicular lymphoma who initiated treatment with Idelalisib within The US Oncology Network," said Presenting Author David Andorsky, MD, a hematologist with RMCC, a practice in The US Oncology Network. "These findings enhance available data on relapsed follicular lymphoma patient outcomes in real-world practice."

The full schedule of affiliated data presentations, including location and author information, can be found here. For more information or to interview a trial investigator, contact Claire Crye at 281.825.9927 or [email protected] or Edie DeVine at 209.814.9564 or [email protected].

On December 5, 2019 Zionexa, a radiopharmaceutical company specialized in the development and commercialization of in-vivo biomarkers for use in guiding targeted therapies in oncology, and PETNET Solutions Inc., a Siemens Healthineers company specializing in the manufacturing and distribution of positron emission tomography (PET) biomarkers, reported that they have entered into an exclusive agreement for the manufacturing and distribution of Zionexa’s new PET diagnostic drug, Fluoroestradiol (FES), which is pending approval by the Food and Drug Administration (FDA) (Press release, Zionexa, DEC 5, 2019, View Source [SID1234551977]).

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Fluoroestradiol (FES) is currently only approved for use in France for the characterization of estrogen receptor status in metastatic breast cancer.

"The Zionexa team is very excited to partner with PETNET in order to produce and distribute FES in the United States and ensure patients with metastatic breast cancer have access to this major innovation," said Bernard Landes, President & CEO Zionexa, "We are proud to work with the world-class team at PETNET to get this important diagnostic biomarker into the hands of clinicians. Studies have shown a high correlation between in-vitro immunohistochemistry assessment of estrogen receptor status and imaging findings using this biomarker. This new biomarker can provide clinicians with additional information to make more informed therapeutic decisions," said Peter Webner Zionexa CEO USA.

Barry Scott, Head of PETNET Solutions, added, "We are delighted to work with Zionexa to provide access to a new PET radiopharmaceutical that yields valuable clinical information to help physicians make treatment decisions. This agreement also allows PETNET to add to our portfolio of oncologic biomarkers and truly enable healthcare providers to practice precision medicine."’

On December 5, 2019 FerGene, a new gene therapy company formed by Ferring Pharmaceuticals and Blackstone Life Sciences, reported positive results from the pivotal Phase 3 clinical trial evaluating nadofaragene firadenovec (rAd-IFN/Syn3), an investigational gene therapy, for the treatment of high-grade, Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) (Press release, FerGene, DEC 5, 2019, View Source [SID1234551976]). FKD Therapies Oy (FKD) has led the development and regulatory filing of nadofaragene firadenovec, which has been studied in 33 centers across the U.S. in collaboration with the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC). The results were presented during the bladder cancer session at the Society of Urologic Oncology 20th Annual Meeting in Washington D.C.

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"These data were part of our submission package to the FDA, and we look forward to continuing to work with the agency to potentially bring nadofaragene firadenovec to patients with BCG unresponsive disease."

The Phase 3 study of 157 patients from the U.S. met its primary endpoint with 53% of CIS ± Ta/T1 patients (carcinoma in situ; bladder cancer that is confined to the superficial layer, with or without concomitant high-grade Ta or T1 papillary disease) achieving a CR at three months, and 24% continuing to show a CR at 12 months. Moreover, the study also demonstrated broad efficacy in this difficult to treat patient population with a 73% HGRF survival in patients with papillary disease at three months and 44% HGRF survival at 12 months. In the study, nadofaragene firadenovec was instilled directly into the patients’ bladder every three months. All responses at 12 months were confirmed by protocol-mandatory five-point biopsies.

Bladder cancer is one of the most frequently occurring cancers with an estimated 699,450 people living with bladder cancer and more than 80,000 new cases diagnosed each year in the U.S. alone.1 In high-grade NMIBC patients, BCG is the standard treatment, and, although effective, over 60% of these tumors eventually re-occur. 2,3

"Currently, patients living with high-grade NMIBC who are unresponsive to BCG have few treatment options and often face bleak outcomes, including complete bladder removal, known as cystectomy," said Colin P. N. Dinney, MD, Professor and Chairman of the Department of Urology at The University of Texas M.D. Anderson Cancer Center. "Cystectomy is a complex and life-altering surgical procedure for patients, so these positive results from the Phase 3 trial of nadofaragene firadenovec are highly promising for patients. It would be gratifying to provide an alternative that addresses the critical unmet need for effective second-line therapy for patients facing radical cystectomy."

In the Phase 3 trial, the most common adverse events (AEs) included fatigue, bladder spasm and discharge around the catheter, micturition urgency, hematuria, chills, fever, headache, painful urination, urinary tract infection, and diarrhea. No grade 4 or 5 treatment-related AEs were reported in the study. Study drug-related AEs were transient and local in nature, with a median duration of less than two days, with the exception of fatigue, which had a median duration of 11 days and urinary frequency which had a median duration of 41 days. There was a 1.9% percent rate of discontinuations due to study drug-related AEs.

"We are pleased with these Phase 3 data results, including the complete response rates and favorable safety profile seen with nadofaragene firadenovec," said Nigel R. Parker4, PhD, of FKD Therapies Oy. "These data were part of our submission package to the FDA, and we look forward to continuing to work with the agency to potentially bring nadofaragene firadenovec to patients with BCG unresponsive disease."

"As a practicing urologist and trial investigator, it’s encouraging to see these types of efficacy and safety results in patients with high-grade NMIBC, an area that’s been in need of new innovative treatment options for more than 20 years," said Neal Shore, MD, FACS, Medical Director, Carolina Urologic Research Center. "These robust clinical results further demonstrate the potential of nadofaragene firadenovec as a valuable treatment option for NMIBC patients."

The U.S. Food and Drug Administration (FDA) has validated FKD’s Biologics License Application (BLA) and granted Priority Review for nadofaragene firadenovec, which previously received Fast Track and Breakthrough Therapy Designations.

About nadofaragene firadenovec

Nadofaragene firadenovec (rAd-IFN/Syn3) is an investigational gene therapy being developed as a treatment for patients with high-grade, BCG unresponsive, NMIBC. It is an adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder every three months. The vector enters the cells of the bladder wall, where, it breaks down, releasing the active gene to do its work. The internal gene/DNA machinery of the cells ‘picks up’ the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient’s own bladder wall cells into multiple interferon microfactories, enhancing the body’s natural defenses against the cancer.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

NMIBC is an early form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.5 It is estimated that there will be 80,000 new cases of bladder cancer in the U.S. in 2019; more than 70% of these cases present as NMIBC.2,6 In patients with high-grade NMIBC, intravesical BCG is the recommended treatment; however, between 30% and 50% cases with high-grade disease will recur.7 The outcome for BCG unresponsive patients is poor, with total cystectomy (complete removal of the bladder) often being the next treatment option.8

On December 5, 2019 NeuClone Pharmaceuticals Ltd (NeuClone), a clinical-stage biopharmaceutical company exclusively focused on developing high-quality biosimilar products, reported that NeuCeptin, a biosimilar candidate of Herceptin (trastuzumab), has successfully met all primary and secondary endpoints in a Phase I clinical trial (Press release, NeuClone Pharmaceuticals, DEC 5, 2019, View Source [SID1234551975]). This includes all pre-specified criteria demonstrating clinical pharmacokinetic (PK) similarity of NeuCeptin, compared to US- and EU-sourced Herceptin. Additionally, the safety and tolerability profiles were equivalent between all three treatment arms.

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Successful completion of the Phase I trial is a significant milestone in the development of a biosimilar as Phase II trials and in some instances Phase III trials are not required to achieve regulatory approval. As of March 2019, no biosimilar found to be highly similar in analytical and human PK studies failed to be approved in the US, EU, Canada or Australia due to clinical inequivalence.1

NeuCeptin is one of several biosimilars developed in partnership between NeuClone and Serum Institute of India Pvt Ltd (Serum Institute), and references trastuzumab, a HER2-targeting monoclonal antibody approved by the FDA and EMA to treat HER2-positive breast and gastric cancer. Trastuzumab was originally commercialised under the brand name Herceptin and generated global sales of USD 7.0 billion in 2018.2

"Positive results from the NeuCeptin trial reflect our dedication to provide high-quality, affordable biologics to a greater number of patients," stated Dr Noelle Sunstrom, CEO and Founder of NeuClone. "Pharmacokinetics are pivotal to the demonstration of biosimilarity and these successful results greatly de-risk this particular program and also validate NeuClone and Serum Institute’s development approach to be replicated for many biosimilars in our pipeline."

"It is extremely pleasing to see the progress of our biosimilar portfolio with co-development partner, NeuClone. We have now achieved successful Phase I results of NeuCeptin (trastuzumab), nearly completed dosing of the Phase I trial for NeuLara (ustekinumab), and palivizumab and pertuzumab biosimilars are both progressing into preclinical and clinical testing," stated Mr. Adar Poonawalla, CEO of Serum Institute. "This clearly speaks of our commitment to make highly cost-effective biosimilars available to all."

NeuClone has 20 biosimilars in various stages of development including clinical-stage candidates NeuCeptin (trastuzumab) and NeuLara (ustekinumab). Several other biosimilars are set to begin clinical development over the coming years. As part of its strategy for biosimilar products, NeuClone remains open to potential development and commercialisation collaborations.

About the Study
The Phase I clinical trial (registration number ACTRN12618001657213) was a randomised, double-blind, single-dose, three-arm study to evaluate the pharmacokinetics (PK) and safety of NeuCeptin compared to Herceptin (trastuzumab). Over 100 healthy volunteers were enrolled in sites across Australia and randomised (1:1:1) to receive either NeuCeptin biosimilar, Herceptin sourced from the US, or Herceptin sourced from the EU, administered as a single intravenous infusion. PK endpoints included: area under the concentration-time curve from first to last timepoint measured (AUC0-last), area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf), and maximum serum concentration (Cmax). The 90% confidence intervals of each endpoint were contained within pre-specified bioequivalence margins of 80% to 125%, for all 3 pairwise comparisons. The trial was conducted under the Therapeutic Goods Administration (TGA) Clinical Trial Notification (CTN) scheme offering a streamlined approach with data output supported by global regulatory agencies such as the EMA and US FDA.